DESCRIPTION (provided by applicant: Relapse is one of the defining features of drug addiction and can be precipitated by a variety of events such as exposure to drugs, drug cues, or stress. Drug taking is operant behavior, and drugs abused by humans function as reinforcers for animals in drug self-administration procedures. Availability of non-drug reinforcement decreases drug self-administration in the laboratory, and behavioral interventions explicitly arranging alternative non-drug reinforcers have been some of the most successful treatments for drug addiction. However, relapse is common when such treatment ends and the alternative reinforcers are no longer provided. Furthermore, loss of non-drug reinforcement outside of treatment might play a role in stress-related relapse more generally. Although existing animal models of relapse are useful for examining the mechanisms of relapse, they do not examine relapse induced by loss of reinforcement for alternative behavior. We have shown that resurgence, another relapse phenomenon in operant conditioning, can provide a useful animal model of drug relapse induced by loss of alternative reinforcement. Resurgence refers to the reappearance of an extinguished operant behavior when an alternative behavior reinforced during extinction is also subsequently placed on extinction. We have demonstrated resurgence of extinguished cocaine self-administration of rats and have developed a quantitative model of resurgence that does a good job accounting for the existing data on resurgence of food-maintained behavior. The theory has proven useful in translation to clinical treatments using alternative reinforcement to reduce problem behavior of children with development disabilities, but has not been examined within the context of drug seeking. This R21 CEBRA project will adapt this theory to addictions research. Specific Aim 1 examines core predictions of the theory about how drug reinforcement and alternative reinforcement interact in the production of relapse. The theory predicts that more frequent or larger alternative reinforcers produce greater relapse when alternative reinforcement is removed. There is some evidence that patients receiving larger vouchers during treatment are more likely to relapse than those achieving similar levels of abstinence with smaller vouchers. Thus, in addition to serving a critical role in adapting the theory to addictions research, completion of this aim could also show how the theory might be useful for informing future interventions for substance abuse. Specific Aim 2 examines two predictions of the theory about how relapse induced by loss of alternative non-drug reinforcement might be reduced. Completion of aim this will serve a critical role in examining the predictive validity of the theory for drug seeking and evaluate its utility in generating novel hypotheses about how relapse might be reduced.